title: Flagellins of Salmonella Typhi and nonpathogenic Escherichia coli are differentially recognized through the NLRC4 pathway in macrophages.
abstract: Flagellin is recognized by both Toll-like receptor (TLR)5 and NAIP5/NLRC4 inflammasome receptors. We hypothesized that the flagellins derived from different bacteria might differentially activate TLR5 and/or NAIP5/NLRC4 signal pathways. To test this, the immune recognition of recombinant flagellins derived from pathogenic Salmonella Typhi (SF) and the nonpathogenic Escherichia coli K12 strain MG1655 (KF) were examined by the activation of TLR5 and NLRC4 pathways in various cell types. While flagellins SF and KF were not distinguishable in activating the TLR5 pathway, KF induced significantly less interleukin-1β production and pyroptotic cell death in peritoneal macrophages than SF, and showed markedly lower efficiency in activating caspase-1 through the NLRC4 pathway than SF. Macrophages may differentially recognize flagellins by intracellular sensors and thereby initiate the immune response to invading pathogenic bacteria. Our findings suggest an active role of flagellin as an important determinant in host differential immune recognition and for the control of bacteria infection.
authors.affiliation: Mucosal Immunity Research Group, State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China.
authors.forename: Jingyi
authors.initials: J
authors.lastname: Yang
authors.forename: Ejuan
authors.initials: E
authors.lastname: Zhang
authors.forename: Fang
authors.initials: F
authors.lastname: Liu
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.forename: Maohua
authors.initials: M
authors.lastname: Zhong
authors.forename: Yaoming
authors.initials: Y
authors.lastname: Li
authors.forename: Dihan
authors.initials: D
authors.lastname: Zhou
authors.forename: Yaoqing
authors.initials: Y
authors.lastname: Chen
authors.forename: Yuan
authors.initials: Y
authors.lastname: Cao
authors.forename: Yang
authors.initials: Y
authors.lastname: Xiao
authors.forename: Benxia
authors.initials: B
authors.lastname: He
authors.forename: Yi
authors.initials: Y
authors.lastname: Yang
authors.forename: Ying
authors.initials: Y
authors.lastname: Sun
authors.forename: Mengji
authors.initials: M
authors.lastname: Lu
authors.forename: Huimin
authors.initials: H
authors.lastname: Yan
mesh_terms: D000818:Animals; D053468:CARD Signaling Adaptor Proteins / Q000378:metabolism*; D018938:Caco-2 Cells; D002135:Calcium-Binding Proteins / Q000378:metabolism*; D020170:Caspase 1 / Q000378:metabolism; D016923:Cell Death; D002478:Cells, Cultured; D004926:Escherichia coli / Q000276:immunology*; D005408:Flagellin / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D058847:Inflammasomes / Q000378:metabolism*; D053583:Interleukin-1beta / Q000378:metabolism; D017737:Macrophages, Peritoneal / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D051192:Receptors, Pattern Recognition / Q000276:immunology / Q000378:metabolism*; D012485:Salmonella typhi / Q000276:immunology*; D015398:Signal Transduction / Q000235:genetics; D051198:Toll-Like Receptor 5 / Q000378:metabolism; D019076:Transgenes / Q000235:genetics; D014435:Typhoid Fever / Q000276:immunology*
chemical_list: D053468:CARD Signaling Adaptor Proteins; D002135:Calcium-Binding Proteins; D058847:Inflammasomes; D053583:Interleukin-1beta; C435692:NLRC4 protein, human; D051192:Receptors, Pattern Recognition; C495346:TLR5 protein, human; D051198:Toll-Like Receptor 5; D005408:Flagellin; D020170:Caspase 1